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Dendritic cells as the terminal stage of monocyte differentiation
K A Palucka1, N Taquet, F Sanchez-Chapuis
1Department of Hematology and Infectious Diseases, Karolinska Hospital and Institute, Stockholm, Sweden.
Abstract:
Monocytes (MO) cultured for > or =5 days with either macrophage-CSF (M-CSF) or granulocyte macrophage (GM)-CSF and IL-4 differentiated without concomitant proliferation into CD14+ macrophages (Mphi) or CD1a+ dendritic cells (DC), respectively. When adherent and nonadherent CD14high Mphi from M-CSF cultures were separated and cultured further in cytokine-free medium or with GM-CSF/IL-4, most cells from both fractions that were exposed to GM-CSF/IL-4 acquired CD1a expression and DC morphology and function. Conversely, GM-CSF/IL-4 withdrawal at day 5 and additional culture of sorted CD1a+ DC for 2 to 7 days in cytokine-free medium led to cells rapidly becoming adherent CD1a-CD14+ Mphi. Replacing GM-CSF/IL-4 with M-CSF hastened the conversion of DC to Mphi without increasing cell numbers. CD1a+CD14-CD83+ mature DC were induced by a > or =2-day exposure to MO-conditioned medium, LPS, or TNF-alpha/IL-1beta. Upon cytokine removal or culture with M-CSF, DC that had been pushed to maturation by conditioned medium or LPS remained stable or died in the new environment. TNF-alpha/IL-1beta-driven DC displayed heterogeneous CD83 expression and could thus be sorted into CD83high and CD83low/- cells; in cytokine-free medium or in M-CSF, most CD83low/- cells converted to Mphi, whereas most CD83high cells remained nonadherent CD1a+CD14- or died and thus appeared truly terminally differentiated. Hence, MO are precursors of Mphi as well as of DC, with each cell type having the capability to convert into the other until late in the differentiation/maturation process. Accordingly, the cytokine environment and the presence of differentiation and/or other stimulatory signals may be the "final decision-making factors" determining whether these cells will acquire DC or Mphi characteristics and function.
Insights
Monocytes differentiate into macrophages or dendritic cells based on cytokine signals. These immune cells can convert between types until late differentiation stages, influenced by their environment.
Area of Science:
- Immunology
- Cell Biology
- Hematopoiesis
Background:
- Monocytes (MO) are key immune cells with potential to differentiate into various lineages.
- Understanding monocyte differentiation into macrophages (Mphi) and dendritic cells (DC) is crucial for immune response modulation.
Purpose of the Study:
- To investigate the plasticity and interconversion potential between monocyte-derived macrophages and dendritic cells.
- To identify the key factors and conditions that dictate monocyte differentiation pathways.
Main Methods:
- Monocytes cultured with macrophage-CSF (M-CSF) or granulocyte-macrophage CSF (GM-CSF) and IL-4.
- Cell sorting based on CD14 and CD1a expression.
- Further culture in cytokine-free media or with different cytokines (M-CSF, GM-CSF/IL-4).
- Induction of mature DC using conditioned media, LPS, or TNF-alpha/IL-1beta.
Main Results:
- M-CSF induced CD14+ Mphi, while GM-CSF/IL-4 induced CD1a+ DC.
- GM-CSF/IL-4 exposure induced DC characteristics in Mphi.
- Cytokine withdrawal or M-CSF treatment caused DC to convert to Mphi.
- Mature DC (CD83+) showed limited conversion, with CD83low/- cells becoming Mphi and CD83high cells terminally differentiating or dying.
Conclusions:
- Monocytes are plastic precursors capable of differentiating into both Mphi and DC.
- Cell fate is determined by cytokine environment and differentiation signals, allowing interconversion until late stages.
- This plasticity highlights the dynamic nature of immune cell differentiation and function.